DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to papers filed on Sept. 29, 2023. The amended claim set filed on Sept. 29, 2023 is being used for examination. Claims 1-9, 13 and 14 are pending and examined on their merits below.
Priority
The application claims foreign priority under 35 U.S.C. 119(a)-(d) to Japanese Patent Application Nos. JP2021-05660 and JP2022-035917, filed on March 30, 2021 and March 9, 2022, respectively.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
The earliest possible priority for the application is March 30, 2021.
Information Disclosure Statement
The information disclosure statement filed Sept. 29, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Claim Rejections - 35 USC § 112/§ 101
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 14 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 14 depends from claim 13, which recites a product (a kit for forming a sheet of mesenchymal stem cells including a water-soluble ascorbic acid derivative, a ROCK inhibitor and a medium). Claim 14 recites “the kit according to claim 13, for use at a concentration of said ascorbic acid species of 0.3 mM or higher.” The claim is indefinite because there are two, conflicting interpretations for this claim: (1) that the recitation of the use if to recite a characterization that the product must meet (e.g. the kit must contain an ascorbic acid species that is capable of being used (intended use) at 0.3 mM or higher); (2) the claim intends to recite the kit of claim 13 used with an ascorbic acid species at 0.3 mM or higher; that is claim 14 intends to recite a process of using the kit of claim 13, wherein, the ascorbic acid species is applied at 0.3 mM or higher.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 14 is also rejected under 35 U.S.C. 101 because, if the claim intends to recite a process of using the kit of claim 13, wherein, the ascorbic acid species is applied at 0.3 mM or higher, then the claimed recitation of a use, without setting forth any steps involved in the process results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967) and Clinical Products, Ltd. V. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
For the purposes of examination, the claim is interpreted as reciting a characterization that the product must meet (e.g. the kit must contain an ascorbic acid species that is capable of being used (intended use) at 0.3 mM or higher).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 5, 9, 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamura et al. (J Periodontal Res., 2014, cited in IDS filed on Sept. 29, 2023) in view of Choi et al. (J Biosce. Bioeng., 2008).
The claims are directed to methods of producing a cell sheet including culturing mesenchymal stem cells (MSCs) in a culture vessel that includes a medium including a water-soluble ascorbic acid derivative at 0.3 mM or higher and ROCK inhibitor.
Nakamura et al. teach culturing human bone-marrow derived MSCs at early passage (2 or 3) in α-minimal essential medium, supplemented with 10% FBS and antibiotics. (Abstract, pg. 364, “Materials and methods: Cells”). The cells were grown from confluence (day 0) and stimulated with MFM (5-Clone medium with human plasma TGF-β1; 0.15 mM AsAP (L-ascorbic acid 2-phosphate) (“a water-soluble ascorbic acid derivative”), 10% FBS and antibiotics, with or without the addition of 10 mM Y-27632 (“ROCK inhibitor”) to form cell sheets. (pg. 364, “Materials and methods: Experimental Conditions”). The cells that were cultured in the presence of the ROCK inhibitor outperformed those that were not, as without the ROCK inhibitor, the cell sheets contracted and reduced their surface area. (pg. 366, “Results”).
Nakamura teaches the medium contains a water-soluble ascorbic acid derivative, AsAP, at 0.15 mM, not the higher 0.3 mM required by the claims.
Choi et al. teach that ascorbic acid influences extracellular matrix production, cell proliferation and differentiation; more specifically Choi et al. investigated the effect of various concentrations of L-ascorbate-2-phosphate (Asc-2-P) on proliferation. (Abstract). Choi et al. teach “As shown in Fig. 1, the cell growth was significantly enhanced in proportion to the increasing Asc-2-P concentration.” The cell proliferation increased with increasing concentration of Asc-2-P, up to 250 µM (0.25 mM) and at 500 µM (0.5 mM), the cell proliferation was lower than at 250 µM (0.25 mM). (pg. 588, “Results,” 1st para. Fig. 1).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the cell sheet preparation method taught by Nakamura et al. to incorporate increasing the concentration of L-ascorbate-2-phosphate (as taught by Choi et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. It would have been obvious to have tried increasing L-ascorbate-2-phosphate to 0.3 mM and to have a reasonable expectation of success because Choi et al. teach that its effect on proliferation increases until 0.25 mM and then decrease at 0.5 mM. Trying a concentration that is a little higher than the 0.25mM (such as 3 or 3.5 mM) would have been obvious, as if the increased proliferative effect continues beyond 0.25 mM, additional benefit can be gained.
With respect to claim 3, Nakamura et al. teach the that the cell sheet is cultured for at least 4 days. (pg. 366 “Results”).
With respect to claim 5, Choi et la. teach the L-ascorbate-2-phosphate is externally (not included as part of a pre-made medium) added. (Abstract).
With respect to claims 7 and 8, Nakamura teaches that MSC cell sheets will be useful in therapeutic endeavors, such as periodontal tissue regeneration, (p. 364, 1st col.). Nakamura et al. further teach that thermoresponsive polymers can be made to remove the cells sheets, but they did not use this method. (pg. 369, 1st & 2nd col.) As no other method of removal is discussed (and Nakamura et al. indicate that trying a thermoresponsive polymer next time is an option), it
would have been obvious to a person of ordinary skill in the after making the cell sheet to have peeled off the cell sheet to physically remove it from the culture vessel and to have stacked the cell sheet on top of another cell sheet. It further would have been obvious to have incubated the combined cell sheets, as making regenerative, therapeutic products would require either a proof of concept that would mean “incubating” the cell sheets in vitro or “incubating” in vivo, as this is exactly what regenerative, therapeutic endeavors require; as such, taking these next steps would have been obvious.
With respect to claim 9, Nakamura et al. teaches the medium contains FBS (“a blood derived component. (pg. 364, “Materials and methods: Experimental Conditions”).
With respect to claims 13 and 14, the combination of Nakamura et al. and Choi et al. would render obvious the claimed combination of having a kit that was designed with the culture of these cell sheets in mind and including ROCK inhibitor, a water soluble ascorbic acid derivative at at least 0.3 mM and a media.
Claim(s) 2, 4, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamura et al. (J Periodontal Res., 2014, cited in IDS filed on Sept. 29, 2023) and Choi et al. (J Biosce. Bioeng., 2008) as applied to claims 1, 3, 5, 9, 13 and 14 above, and further in view of Shotorbani et al. (J Material Sci, 2018).
Nakamura et al. do not teach the addition of a second ascorbic acid derivative, nor do they teach the MSCs are derived from fat tissue or that the culture vessel is coated with a temperature-sensitive polymer.
Shotobani et al. teach that culturing MSCs derived from adipose tissue, ASCs, (“derived from fat tissue”) in the presence of vitamin C and the secretome of ASCs on thermosensitive P(NIPA Am-MAA) hydrogels, lead to a the ability to rapidly remove the cell sheets without enzymatic treatment when desired. (Abstract).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the method taught by Nakamura et al. to incorporate an additional vitamin C derivative, using adipose-derived MSCs and coating the culture vessel with a temperature-sensitive polymer (as taught by Shotobani et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating these modification would have led to predictable results with a reasonable expectation of success because the references are all directed to making cell sheets which incorporate additional functionality. With respect to the ascorbic acid being a derivative of vitamin C, this would have been an obvious substitution to make, as vitamin C is known to degrade quickly (see Choi et al.) and become toxic to cells; as such, when used for longer term culturing, selection of a second ascorbic acid derivative would have been an obvious choice.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TERESA E KNIGHT whose telephone number is (571)272-2840. The examiner can normally be reached Monday-Friday 9-4.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TERESA E KNIGHT/ Primary Examiner, Art Unit 1634